The publication of Bovin et al (2005) discloses synthetic molecules that spontaneously and stably incorporate into lipid bilayers, including cell membranes. The synthetic molecules consist of a functional moiety (F), such as a mono-, di-, tri- or oligosaccharide, covalently linked to a lipid moiety (L), such as phosphatidylethanolamine, via a spacer (S). The spacer is selected to provide synthetic molecules that readily disperse in water without the use of detergents or solvents and may be used to effect qualitative and quantitative changes in the expression of cell surface antigens. The publication discloses the use of these synthetic molecules in a method of preparing red blood cells expressing controlled amounts of blood group-related glycans. These modified or transformed cells (now referred to as ‘kodecytes’) may be used as positive controls in the quality assurance of blood group typing reagents.
The publication of Bovin et al (2009) discloses functional lipid constructs consisting of a functional moiety (F) covalently linked to a lipid (L) moiety via an elongate spacer (S). In common with the synthetic molecules disclosed in the publication of Bovin et al (2005), the constructs spontaneously incorporate into cell membranes despite being readily dispersible in water. The constructs provide the additional advantage that the functional moiety (F) is presented at a distance from the surface of the cell membrane. The publication of Bovin et al (2010) discloses constructs where the functional moiety (F) is a ligand for a receptor. The publication discloses muitiligand constructs of a tri- or tetra-antennary structure. The inter-ligand spacing of the constructs is intended to promote multivalent interactions between the ligands and the ligand-binding protein or receptor.
Ligand binding proteins include glycan binding proteins (GBPs). These proteins play important roles in mechanisms of immunity and microbe-host interactions. GBPs are present in the sera of all individuals. The immune system depends largely on the presence of a competent and well-equipped repertoire of these GBPs. Many of the GBPs are natural antibodies (NAbs) that bind to glycan ligands expressed in normal human tissues (auto-antibodies). However, NAbs may also be associated with a number of diseases, e.g. the antibodies to tumour-associated carbohydrate antigens (TACA). Transformation of cells from healthy to pre-malignant and malignant is associated with the appearance of abnormal glycosylation on proteins and lipids presented on the surface of the cells. Changes in the NAb profile of an individual can therefore be associated with the onset and progress of a number of diseases, including cancer.
It is an object of the present invention to provide multivalent ligand-lipid constructs for use in the preparation of kodecytes with increased avidity for ligand binding proteins. The preceding object is to be read in the alternative with the object at least to provide a useful choice.